PMID:15845892

Citation	He, Q, Madsen, M, Kilkenney, A, Gregory, B, Christensen, EI, Vorum, H, Højrup, P, Schäffer, AA, Kirkness, EF, Tanner, SM, de la Chapelle, A, Giger, U, Moestrup, SK and Fyfe, JC (2005) Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood 106:1447-53
Abstract	Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal malabsorption of cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight proteins. Vital insight into the molecular pathology of I-GS has been obtained from studies of dogs with a similar syndrome. In this work, we show that I-GS segregates in a large canine kindred due to an in-frame deletion of 33 nucleotides in exon 10 of AMN. In a second, unrelated I-GS kindred, affected dogs exhibit a homozygous substitution in the AMN translation initiation codon. Studies in vivo demonstrated that both mutations abrogate AMN expression and block cubilin processing and targeting to the apical membrane. The essential features of AMN dysfunction observed in vivo are recapitulated in a heterologous cell-transfection system, thus validating the system for analysis of AMN-cubilin interactions. Characterization of canine AMN mutations that cause I-GS establishes the canine model as an ortholog of the human disorder well suited to studies of AMN function and coevolution with cubilin.
Links	PubMed PMC1895201 Online version:10.1182/blood-2005-03-1197
Keywords	Animals; Codon, Initiator; DNA Mutational Analysis; Dogs; Exons; Intestinal Absorption/genetics; Microvilli/metabolism; Models, Animal; Mutation; Pedigree; Proteins; Receptors, Cell Surface/metabolism; Sequence Deletion; Syndrome; Vitamin B 12 Deficiency/etiology; Vitamin B 12 Deficiency/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CANLF:AMNLS		GO:0016324: apical plasma membrane	ECO:0000315:		C		Figure 5C uses immunoperoxidase staining to show that in wildtype dog kidney cells, amnionless and cubilin are localized to the plasma membrane, while in cells with mutant AMN, the protein complex is not localized there	complete CACAO 9856
CANLF:AMNLS	part_of	GO:0016324: apical plasma membrane	ECO:0000315: mutant phenotype evidence used in manual assertion		C		Seeded From UniProt	complete

References

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